Genes that control complex phenotypic traits are often difficult to map and even more difficult to identify. However, the identification of these genes could have important implications in our understanding of certain disease processes and their etiologies. The specific aims of this proposal are designed to investigate the use of knockout/congenic strains of mice for the mapping and identification of genes involved in complex traits. Knockout/congenic strains of mice are ones where a target locus has been ablated by homologous recombination in embryonic stem (ES) cells and which have also been backcrossed at least 8 times to an inbred strain, usually B6. Thus, these strains differ from their inbred partner not only at the target locus (target of the ablation) but also at the flanking region derived from the ES cell genotype (usually of 129 origin). We would like to use these strains to investigate the polymorphic differences that exist between the B6 and 129 strains. We present preliminary data that these knockout/congenic strains may be useful in this regard. Our specific aims are: (1) to determine the phenotypic differences that exist between knockout/congenic strains and their inbred partners. Here, we will focus on mouse behavioral traits since they are difficult to map by more conventional techniques; (2) to identify and confirm that some of these differences between knockout/congenic strains and their inbred partners are due to residual passenger 129 genetic material linked to the target or differential locus. Subcongenic strains will be made for further refinement of the region and to be used as future tools for the eventual positional cloning of these genes. [unreadable] [unreadable]